Giuseppe Tarantino: Genomic Heterogeneity and Ploidy predict resistance to Anti-PD-1 Therapy in Metastatic Melanoma
Giuseppe Tarantino, Research Fellow at Dana-Farber Cancer Institute, shared on LinkedIn:
“Excited to share our latest publication!
In this study, we explored how genomic heterogeneity and ploidy can predict intrinsic resistance to anti-PD-1 immune checkpoint blockade (ICB) in metastatic melanoma patients.
Key findings:
– Low ploidy and high heterogeneity consistently identify patients unlikely to respond to single-agent aPD-1 therapy across multiple independent cohorts.
– We developed a highly interpretable predictive model based on just these two features. The model achieves 97% specificity and 90% positive predictive value (PPV), offering a practical tool to personalize immunotherapy strategies.
– Timing of whole-genome doubling (WGD) plays a crucial role in resistance.
– Genomic heterogeneity and ploidy are independent of clinical features (e.g., presence of brain metastases, LDH levels) and outperform traditional biomarkers like TMB and IFN-γ signatures as predictors of therapy response.
– Paired Targeted NGS panels can potentially estimate heterogeneity and ploidy, paving the way for broader clinical adoption.
Check out the full paper here.”
Authors: Giuseppe Tarantino, Cora A. Ricker, Annette Wang, William Ge, Tyler J. Aprati, Amy Y. Huang, Shariq Madha, Jiajia Chen, Yingxiao Shi, Marc Glettig, Catherine H. Feng, Dennie T. Frederick, Samuel Freeman, Marta M. Holovatska, Michael P. Manos, Lisa Zimmer, Alexander Rösch, Anne Zaremba, Elisabeth Livingstone, Jacob C. Jameson, Soroush Saghafian, Andrew Lee, Karena Zhao, Luc G.T. Morris, Brendan Reardon, Jihye Park, Haitham A. Elmarakeby, Bastian Schilling, Anita Giobbie-Hurder, Natalie I. Vokes, Elizabeth I. Buchbinder, Keith T. Flaherty, Rizwan Haq, Catherine J. Wu, Genevieve M. Boland, F. Stephen Hodi, Eliezer M. Van Allen, Dirk Schadendorf, and David Liu
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